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BACKGROUND: Many survivors of a first primary cancer (FPCs) are at risk of developing a second primary cancer (SPC), with effects on patient prognosis. Primary cancers have different frequencies of specific SPC development and the development of SPCs may be closely related to the FPC. The aim of this study was to explore possible correlations between SPCs and FPCs. METHODS: Relevant literature on SPCs was retrospectively searched and screened from four databases, namely, PubMed, EMBASE, Web of Science, and PMC. Data on the number of patients with SPC in 28 different organ sites were also collected from The Surveillance, Epidemiology, and End Results (SEER) 8 Registry and NHANES database. RESULTS: A total of 9 617 643 patients with an FPC and 677 430 patients with an SPC were included in the meta-analysis. Patients with a first primary gynaecological cancer and thyroid cancer frequently developed a second primary breast cancer and colorectal cancer. Moreover, those with a first primary head and neck cancer, anal cancer and oesophageal cancer developed a second primary lung cancer more frequently. A second primary lung cancer and prostate cancer was also common among patients with first primary bladder cancer and penile cancer. Patients with second primary bladder cancer accounted for 56% of first primary ureteral cancer patients with SPCs. CONCLUSIONS: This study recommends close clinical follow-up, monitoring and appropriate interventions in patients with relevant FPCs for better screening and early diagnosis of SPCs.
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Neoplasias Pulmonares , Segunda Neoplasia Primária , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Humanos , Incidência , Segunda Neoplasia Primária/epidemiologia , Inquéritos Nutricionais , Neoplasias da Próstata/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
As a nontraditional T-cell subgroup, γδT cells have gained popularity in the field of immunotherapy in recent years. They have extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious in tumor patients, have become pioneer drugs in the field of tumor immunotherapy since they were incorporated into clinical practice. In addition, γδT cells that have infiltrated into tumor tissues are found to be in a state of exhaustion or anergy, and there is upregulation of many immune checkpoints (ICs) on their surface, suggesting that γδT cells have a similar ability to respond to ICIs as traditional effector T cells. Studies have shown that targeting ICs can reverse the dysfunctional state of γδT cells in the tumor microenvironment (TME) and exert antitumor effects by improving γδT-cell proliferation and activation and enhancing cytotoxicity. Clarification of the functional state of γδT cells in the TME and the mechanisms underlying their interaction with ICs will solidify ICIs combined with γδT cells as a good treatment option.
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Neoplasias , Linfócitos T , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imunoterapia , Microambiente TumoralRESUMO
Immune checkpoint inhibitors (ICIs) combined with the anti-angiogenesis drug bevacizumab is one of the future directions of immunotherapy. However, the potential adverse drug reactions (ADRs) caused by combination therapy remain unclear. Current research on ADRs of combination therapy in cancer patients is extremely limited. Our study aims to help determine the safety of combination therapy. We downloaded the ADR reports on combination therapy, from the first quarter of 2012 to the fourth quarter of 2021, from the FDA adverse event reporting system (FAERS) database and conducted a large-scale retrospective study. The ADR signals were monitored by reporting odds ratio (ROR) and analyzing the risk of different ADRs in patients with Pan-cancer. A total of 2094 cases were selected, after excluding duplicate data and the use of chemotherapy drugs. We evaluated the risk of ADR in Pan-cancer patients. Combination therapy was an independent risk factor for adverse drug reactions associated with interstitial lung disease (OR: 8.62; 95% CI: 6.14-12.10, P < .0001), hypertension (OR: 1.35; 95% CI: 1.11-1.65, P < .01) and gastrointestinal bleeding (OR: 3.16; 95% CI: 2.21-4.51, P < .0001). A subgroup analysis revealed that the risk of endocrine system-related ADRs was elevated in patients receiving different combination therapies or with certain tumor types. We retrospectively studied the ADR of combination therapy in Pan-cancer patients and analyzed the distribution characteristics of ADR from the perspectives of treatment strategy and cancer types to provide recommendations for the individualized management of patients receiving combination therapy.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias , Humanos , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos , Bevacizumab/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias/tratamento farmacológicoRESUMO
ABSTRACT: Craniomaxillofacial surgery has the characteristics of complex anatomical structure, narrow surgical field, and easy damage to nerves, blood vessels, and other structures. Compared with the traditional bare-hand operation, robot-assisted craniofacial surgery is expected to achieve a more stable and accurate surgical operation. So we have developed a robot-assisted craniofacial surgery system. A compact mechanism design was adopted for the robot system, integrates with visual and force perception modules. The motion analysis and working space analysis are carried out on the mechanical structure. The binocular vision module is integrated and the robot hand-eye calibration process was completed. The target tracking method based on staple is used to achieve tracking and monitoring of the target area. A distributed robot control system based on CAN bus technology is designed, and a position-based visual servo control method is adopted. Then the precision test of the robot system prototype and the drilling experiment of the 3D printed mandible model were carried out. The average pixel error of the vision module is 0.15 pixels. Based on the staple tracking method, the average center error rate of the image is 0.3175âmm, and the overlap rate is 88.76%. The drilling experiment of the mandible model showed that the average entrance position error is 1.76â±â0.36âmm, the average target position error is 1.62â±â0.27âmm, and the angle error is 5.36â±â0.31 degrees. The designed craniofacial robot system can better assist surgeons to complete the mandibular osteotomy.
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Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Mandíbula , Osteotomia MandibularRESUMO
Mandibular angle split osteotomy (MASO) is a procedure widely used for prominent mandibular angles. However, conventional mandibular plastic surgery is invasive and high risk. It may induce postoperative neurosensory disturbance of the inferior alveolar nerve, fractures and infection due to the complexity of the anatomical structure and the narrow surgical field of view. The success rate of MASO surgery usually depends on the clinical experience and skills of the surgeon. To evaluate the performance of inexperienced plastic surgeons conducting this surgery, a self-developed and constructed robot system based on augmented reality is used. This robot system provides for sufficient accuracy and safety within the clinical environment. To evaluate the accuracy and safety of MASO surgery, an animal study using this robot was performed in the clinical room, and the results were then evaluated. Four osteotomy planes were successfully performed on two dogs; that is, twenty tunnels (each dog drilled on bilaterally) were drilled in the dogs' mandible bones. Errors at entrance and target points were 1.04 ± 0.19 and 1.22 ± 0.24 mm, respectively. The angular error between the planned and drilled tunnels was 6.69° ± 1.05°. None of the dogs experienced severe complications. Therefore, this technique can be regarded as a useful approach for training inexperienced plastic surgeons on the various aspects of plastic surgery. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Osteotomia Mandibular/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Plástica/instrumentação , Animais , Cães , Osteotomia Mandibular/instrumentação , Modelos Animais , Cuidados Pré-Operatórios/métodos , Cirurgia Plástica/métodos , Análise e Desempenho de TarefasRESUMO
BACKGROUND: Mandible plastic surgery plays an important role in conventional plastic surgery. However, its success depends on the experience of the surgeons. In order to improve the effectiveness of the surgery and release the burden of surgeons, a mandible plastic surgery assisting robot, based on an augmented reality technique, was developed. MATERIAL AND METHODS: Augmented reality assists surgeons to realize positioning. Fuzzy control theory was used for the control of the motor. During the process of bone drilling, both the drill bit position and the force were measured by a force sensor which was used to estimate the position of the drilling procedure. RESULTS: An animal experiment was performed to verify the effectiveness of the robotic system. The position error was 1.07 ± 0.27 mm and the angle error was 5.59 ± 3.15°. The results show that the system provides a sufficient accuracy with which a precise drilling procedure can be performed. In addition, under the supervision's feedback of the sensor, an adequate safety level can be achieved for the robotic system. CONCLUSION: The system realizes accurate positioning and automatic drilling to solve the problems encountered in the drilling procedure, providing a method for future plastic surgery.
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Mandíbula/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Procedimentos Cirúrgicos Robóticos/instrumentação , Cirurgia Plástica/instrumentação , Animais , Cães , Lógica Fuzzy , SuínosRESUMO
Herein, the first acceptorless dehydrogenation of tetrahydroquinolines (THQs), indolines, and other related N-heterocycles, by merging visible-light photoredox catalysis and cobalt catalysis at ambient temperature, is described. The potential applications to organic transformations and hydrogen-storage materials are demonstrated. Primary mechanistic investigations indicate that the catalytic cycle occurs predominantly by an oxidative quenching pathway.
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Co-occurrence and mutual exclusivity of genomic alterations may reflect the existence of genetic interactions, potentially shaping distinct biological phenotypes and impacting therapeutic response in breast cancer. However, our understanding of them remains limited. Herein, we investigate a large-scale multi-omics cohort (n = 873) and a real-world clinical sequencing cohort (n = 4,405) including several clinical trials with detailed treatment outcomes and perform functional validation in patient-derived organoids, tumor fragments, and in vivo models. Through this comprehensive approach, we construct a network comprising co-alterations and mutually exclusive events and characterize their therapeutic potential and underlying biological basis. Notably, we identify associations between TP53mut-AURKAamp and endocrine therapy resistance, germline BRCA1mut-MYCamp and improved sensitivity to PARP inhibitors, and TP53mut-MYBamp and immunotherapy resistance. Furthermore, we reveal that precision treatment strategies informed by co-alterations hold promise to improve patient outcomes. Our study highlights the significance of genetic interactions in guiding genome-informed treatment decisions beyond single driver alterations.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Genômica , Resultado do Tratamento , Fenótipo , MutaçãoRESUMO
Triple-negative breast cancer (TNBC) is an aggressive disease characterized by remarkable intratumor heterogeneity (ITH), which poses therapeutic challenges. However, the clinical relevance and key determinant of ITH in TNBC are poorly understood. Here, we comprehensively characterized ITH levels using multi-omics data across our center's cohort (n = 260), The Cancer Genome Atlas cohort (n = 134), and four immunotherapy-treated cohorts (n = 109). Our results revealed that high ITH was associated with poor patient survival and immunotherapy resistance. Importantly, we identified zinc finger protein 689 (ZNF689) deficiency as a crucial determinant of ITH formation. Mechanistically, the ZNF689-TRIM28 complex was found to directly bind to the promoter of long interspersed element-1 (LINE-1), inducing H3K9me3-mediated transcriptional silencing. ZNF689 deficiency reactivated LINE-1 retrotransposition to exacerbate genomic instability, which fostered ITH. Single-cell RNA sequencing, spatially resolved transcriptomics and flow cytometry analysis confirmed that ZNF689 deficiency-induced ITH inhibited antigen presentation and T-cell activation, conferring immunotherapy resistance. Pharmacological inhibition of LINE-1 significantly reduced ITH, enhanced antitumor immunity, and eventually sensitized ZNF689-deficient tumors to immunotherapy in vivo. Consistently, ZNF689 expression positively correlated with favorable prognosis and immunotherapy response in clinical samples. Altogether, our study uncovers a previously unrecognized mechanism underlying ZNF689 deficiency-induced ITH and suggests LINE-1 inhibition combined with immunotherapy as a novel treatment strategy for TNBC.
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Neoplasias de Mama Triplo Negativas , Humanos , Imunoterapia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Fatores de Transcrição/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Resistencia a Medicamentos Antineoplásicos/genéticaRESUMO
BACKGROUND: Seasonal allergic rhinitis (SAR) is a chronic inflammatory disease for which the molecular mechanism is unclear. METHODS: Whole blood, CD4+ T cells in peripheral blood mononuclear cells (PBMCs), and CD4+ T cells in nasal mucosa from SAR-related datasets (GSE43497, GSE50223, and GSE49782) were downloaded from the Gene Expression Omnibus (GEO) database. Differences in SAR-associated immune cell infiltration in the PBMCs were analyzed using the CIBERSORT algorithm. Differential gene expression analysis was conducted between different groups. Gene set enrichment analysis (GSEA) was performed using the clusterProfiler package to explore functional changes in signaling pathways. RESULTS: There was a significant increase in the proportion of CD8+ T cells and a significant decrease in the proportion of neutrophils in the whole blood of SAR patients after allergen challenge compared to SAR patients after diluent challenge. This pattern was also found in SAR patients compared to healthy controls (HCs) by flow cytometry. The NF-κB and Toll-like receptor signaling pathways were enriched in SAR patients following allergen challenge. The expression of CD4+ T cell marker genes and associated cytokines significantly differed between allergen-treated SAR patients, diluent-treated SAR patients and HCs. We also observed heightened CD4+ T cell related genes, cytokines and pathways activation in the nasal mucosa region of SAR patients after allergen challenge. CONCLUSION: Our analysis revealed that T cell receptor signaling pathways, T helper 1 (Th1) /T helper 2 (Th2) cell differentiation may contribute to the development of SAR. The present study is the first bioinformatic analysis to quantify immune cell infiltration and identify underlying SAR mechanisms from combined microarray data and provides insight for further research into the molecular mechanisms of SAR.
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Rinite Alérgica Sazonal , Rinite Alérgica , Humanos , Rinite Alérgica Sazonal/genética , Linfócitos T CD8-Positivos , Leucócitos Mononucleares/metabolismo , Alérgenos , Citocinas/genética , Rinite Alérgica/genéticaRESUMO
Background: Small-cell lung cancer (SCLC) is characterized by its high malignancy and is associated with a poor prognosis. In the early stages of the disease, platinum-based chemotherapy is the recommended first-line treatment and has demonstrated efficacy. However, SCLC is prone to recurrence and is generally resistant to chemotherapy in its later stages. Methods: Here, we collected samples from SCLC patients who received platinum-based chemotherapy, performed genomic and transcriptomic analyses, and validated our results with publicly available data. Results: SCLC patients with DNA polymerase binding pathway mutations had an improved prognosis after platinum chemotherapy compared with patients without such mutations. Patients in the mutant (MT) group had higher infiltration of T cells, B cells, and M1 macrophages compared with patients without DNA polymerase binding pathway mutations. Conclusions: DNA polymerase binding pathway mutations can be used as prognostic markers for platinum-based chemotherapy in SCLC.
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There is an urgent need for markers to predict the efficacy of different chemotherapy drugs. Herein, we examined whether microsatellite instability (MSI) status can predict tumor multidrug sensitivity and explored the underlying mechanisms. We downloaded data from several public databases. Drug sensitivity was compared between the high microsatellite instability (MSI-H) and microsatellite-stable/low microsatellite instability (MSS/MSI-L) groups. In addition, we performed pathway enrichment analysis and cellular chemosensitivity assays to explore the mechanisms by which MSI status may affect drug sensitivity and assessed the differences between drug-treated and control cell lines. We found that multiple MSI-H tumors were more sensitive to a variety of chemotherapy drugs than MSS/MSI-L tumors, and especially for CRC, chemosensitivity is enhanced through the downregulation of DDR pathways such as NHEJ. Additional DNA damage caused by chemotherapeutic drugs results in further downregulation of DDR pathways and enhances drug sensitivity, forming a cycle of increasing drug sensitivity.
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Background: With the increasing use of immune checkpoint inhibitors (ICIs) for tumour immunotherapy, the immune-related adverse events (irAEs) caused by their collateral effect on the immune system pose a key challenge for the clinical application of ICIs. Psychiatric adverse events are a class of adverse events associated with ICIs that are realistically observed in the real world. We aim to provide a comprehensive study and summary of psychiatric adverse events associated with ICIs. Methods: We obtained ICI adverse reaction reports during January 2012-December 2021 from the FDA Adverse Event Reporting System (FAERS) database. ICI reports underwent screening to minimize the influence of other adverse reactions, concomitant medications, and indications for medication use that may also contribute to psychiatric disorders. Disproportionality analysis was performed to find psychiatric adverse events associated with ICIs by comparing ICIs with the full FAERS database using the reporting odds ratio (ROR). Influencing factors were explored based on univariate logistic regression analysis. Finally, the Cancer Genome Atlas (TCGA) pan-cancer transcriptome data were combined to explore the potential biological mechanisms associated with ICI-related pAEs. Findings: Reports of psychiatric adverse events accounted for 2.71% of the overall ICI adverse event reports in the FAERS database. Five categories of psychiatric adverse events were defined as ICI-related psychiatric adverse events (pAEs). The median age of reports with ICI-related pAEs was 70 (interquartile range [IQR] 24-95), with 21.54% of reports having a fatal outcome. Cases with indications for lung cancer, skin cancer and kidney site cancer accounted for the majority. The odds of ICI-related pAEs increased in older patients (65-74: OR = 1.44 [1.22-1.70], P < 0.0001: ≥75: OR = 1.84 [1.54-2.20], P < 0.0001). The occurrence of ICI-related pAEs may be related to NOTCH signalling and dysregulation of synapse-associated pathways. Interpretation: This study investigated psychiatric adverse events highly associated with ICI treatment, their influencing factors and potential biological mechanisms, which provides a reliable basis for further in-depth study of ICI-related pAEs. However, as an exploratory study, our findings need to be further confirmed in a large-scale prospective study. Funding: This work was supported by the Natural Science Foundation of Guangdong Province (2018A030313846 and 2021A1515012593), the Science and Technology Planning Project of Guangdong Province (2019A030317020) and the National Natural Science Foundation of China (81802257, 81871859, 81772457, 82172750 and 82172811). Guangdong Basic and Applied Basic Research Foundation (Guangdong - Guangzhou Joint Fouds) (2022A1515111212). This work was supported by Key Research and Development Projects of Sichuan Science and Technology (2022YFS0221, 2022YFS0074, 2022YFS0156 and 2022YFS0378). Sichuan Provincial People's Hospital Hospital Young Talent Fund (2021QN08).
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Introduction: Neuroendocrine (NE) transformation has been reported in patients with ALK-rearranged NSCLC after ALK inhibition, but unlike EGFR-mutant NSCLC, the exact mechanism of NE transformation in ALK-rearranged NSCLC is poorly studied. Methods: We collected the matched pre- and post-transformation samples from a patient with ALK-rearranged lung adenocarcinoma (LUAD) and performed targeted panel sequencing, whole exome sequencing, and bulk RNA sequencing. Results: Multiple mutations were shared between the pretransformation and post-transformation samples. Neither RB1 nor TP53 mutation was detected, but CDKN2A deletion and CDK4 amplification were found instead. Mismatch repair-associated mutational signature was significantly enriched after transformation. Genes associated with Notch signaling and PI3K/AKT pathway were significantly up-regulated, whereas genes related to lymphocyte activation and NF-kB signaling were down-regulated. Signatures relating to homologous recombination, mismatch repair, and Notch signaling pathways were enriched, which were further validated in The Cancer Genome Atlas cohorts. Macrophages M2 were found to have prominently higher abundance in the tumor immune microenvironment after NE transformation. Conclusions: The mechanism of NE transformation in ALK-rearranged LUAD may be different from that in EGFR-mutant LUAD.
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BACKGROUND: The complex anatomical structure, limited field of vision, and easily damaged nerves, blood vessels, and other anatomical structures are the main challenges of a cranio-maxillofacial (CMF) plastic surgical robot. Bearing these characteristics and challenges in mind, this paper presents the design of a master-slave surgical robot system with a force feedback function to improve the accuracy and safety of CMF surgery. METHODS: A master-slave CMF surgical robot system based on force feedback is built with the master tactile robot and compact slave robot developed in the laboratory. Model-based master robot gravity compensation and force feedback mechanism is used for the surgical robot. Control strategies based on position increment control and ratio control are adopted. Aiming at the typical mandibular osteotomy in CMF surgery, a scheme suitable for robot-assisted mandibular osteotomy is proposed. The accuracy and force feedback function of the robot system under direct control and master-slave motion modes are verified by experiments. RESULTS: The drilling experiment of the mandible model in direct control mode shows that the average entrance point error is 1.37 ± 0.30 mm, the average exit point error is 1.30 ± 0.25 mm, and the average posture error is 2.27° ± 0.69°. The trajectory tracking and in vitro experiment in the master-slave motion mode show that the average position following error is 0.68 mm, and the maximum force following error is 0.586 N, achieving a good tracking and force feedback function. CONCLUSION: The experimental results show that the designed master-slave CMF robot can assist the surgeon in completing accurate mandibular osteotomy surgery. Through force feedback mechanism, it can improve the interaction between the surgeon and the robot, and complete tactile trajectory movements.
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Desenho de Equipamento , Face/cirurgia , Retroalimentação , Osteotomia Mandibular , Fenômenos Mecânicos , Procedimentos Cirúrgicos Robóticos , Cirurgia Assistida por Computador , Tato , HumanosRESUMO
Genioplasty is the main way to treat diseases such as chin asymmetry, dysplasia and overdevelopment, which involve the three-dimensional direction abnormalities of the chin. Since this kind of surgery mainly uses intraoral incisions, the narrow surgical field of intraoral incisions and the surrounding important neurovascular tissues make it easy for complications, to occur during the osteotomy process, which results in greater surgical risks. The first craniofacial-plastic surgical robot (CPSR-I) system is developed to complete the precise positioning and improve the surgeon's force perception ability. The Kalman filtering method is adopted to reduce the interference of sensor signal noise. An adaptive fuzzy control system, which has strong robustness and adaptability to the environment, is designed to improve the stability of robot-assisted surgical operations. To solve the problem of the depth perception, we propose an automatic bone drilling control strategy that combines position and force conditions to ensure that the robot can automatically stop when the bone is penetrated. On the basis of model surgery and animal experiments, preliminary experiments were carried out clinically. Based on the early results of 6 patients, the robot-assisted approach appears to be a safe and effective strategy for genioplasty.
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Queixo/cirurgia , Mentoplastia/métodos , Mandíbula/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Mandíbula/fisiopatologia , Osteotomia/normas , Procedimentos de Cirurgia Plástica/normas , Robótica , Adulto JovemRESUMO
Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of metastatic urothelial carcinoma (mUC), a dominant type of bladder cancer (BC). Previous studies have shown an association between gene mutations in the DNA damage response (DDR) pathway and the immunotherapy response in mUC but have neglected the effect of the activation level of the DDR pathway on the ICI response in mUC. A published immunotherapy cohort with genome, transcriptome and survival data for 348 mUC patients was used. An external cohort (The Cancer Genome Atlas Bladder Cancer) and the GSE78220 cohort were used for validation. The activation level of the DDR pathway was quantified using single-sample gene set enrichment analysis (ssGSEA). Further analysis on the genome, immunogenicity, and the immune microenvironment was conducted using the DDR ssGSEA enrichment score-high (DSSH) group and the DDR ssGSEA enrichment score-low (DSSL) group. In the mUC cohorts, the DSSH group was associated with longer overall survival times (P=0.026; Hazard ratio=0.67; 95%CI: 0.46-0.95). The DSSH group was also associated with higher tumor mutation burden, neoantigen load, immune-activated cell patterns, and immune-related gene expression levels. The GSEA results indicated an immune activation state in DSSH group, which correlated with a down-regulation in the transforming growth factor ß receptor signaling pathway. Our study suggests that the activation level of the DDR pathway may be a novel predictive marker for immunotherapy efficacy in patients with mUC.
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Carcinoma/tratamento farmacológico , Dano ao DNA , Reparo do DNA , Inibidores de Checkpoint Imunológico/uso terapêutico , Fator de Crescimento Transformador beta/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Urotélio/efeitos dos fármacos , Carcinoma/genética , Carcinoma/imunologia , Carcinoma/metabolismo , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica , Transdução de Sinais , Transcriptoma , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento , Microambiente Tumoral , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Urotélio/metabolismo , Urotélio/patologiaRESUMO
Melanoma refers to a pigmented nevus with malignant changes. The preferred treatment for primary melanoma is surgical excision and postoperative radiotherapy, but the prognosis is poor. Immune checkpoint inhibitors (ICIs) have been remarkably successful in different types of cancers, but not all cancer patients can benefit from it. Therefore, it is essential to find predictable biomarkers and improve the accuracy of treatment. In this study, we used survival analysis, gene panorama analysis, immune cell enrichment analysis, TMB analysis, and GSEA to demonstrate that SCN4A gene mutations may be used as one of the indicators to predict the prognosis of melanoma patients undergoing ICI treatment. The research further indicates that SCN4A gene mutations improve the prognosis of ICI treatment. It is hoped that the effect of SCN4A on immunogenicity and tumor immunity can be demonstrated to further suggest the effect of this gene on the efficacy of ICIs.
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Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Melanoma/genética , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Inibidores de Checkpoint Imunológico/imunologia , Imunoterapia/tendências , Masculino , Melanoma/tratamento farmacológico , Melanoma/imunologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologiaRESUMO
BACKGROUND: Augmented reality (AR)-based navigation surgery has evolved to be an advanced assisted technology. The aim of this study is to manifest the accuracy of AR navigation for the intraoperative mandibular angle osteotomy by comparing the navigation with other interventional techniques. METHODS: A retrospective study was conducted with 93 post-surgical patients with mandibular angle hypertrophy admitted at our plastic and reconstructive surgery department between September 2011 and June 2016. Thirty-one patients received osteotomy conducted using a navigation system based on augmented reality (AR group), 28 patients received osteotomy conducted using individualised templates (IT group) and the remaining 34 patients received osteotomy performed by free hand (free-hand group). The post-operative computed tomography (CT) images were reviewed and analysed by comparing with pre-surgical planning generated by three-dimensional (3D) software. The preparation time, cutting time, whole operating time and discrepancy in osteotomy lines were measured. RESULTS: The preparation time was much shorter for the free-hand group than that for the AR group and the IT group (P < 0.01). However, no significant difference in the whole operating time was observed among the three groups (P > 0.05). In addition, the discrepancy in osteotomy lines was lower for the AR group and in the IT group than for the free-hand group (P < 0.01). CONCLUSION: The navigation system based on AR has a higher accuracy, more reliability and better user friendliness for some particular clinical procedures than for other techniques, which has a promising clinical prospect.
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Imageamento Tridimensional , Mandíbula/cirurgia , Osteotomia Mandibular/métodos , Procedimentos de Cirurgia Plástica/métodos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Interface Usuário-Computador , Adulto , Feminino , Seguimentos , Humanos , Mandíbula/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Surgical robots lack force feedback, which may lead to operation errors. In order to improve surgical outcomes, this research developed a new master-slave surgical robot, which was designed with an integrated force sensor. METHODS: The new structure designed for the master-slave robot employs a force feedback mechanism. A six-dimensional force sensor was mounted on the tip of the slave robot's actuator. Sliding model control was adopted to control the slave robot. According to the movement of the master system manipulated by the surgeon, the slave's movement and the force feedback function were validated. RESULTS: The motion was completed, the standard deviation was calculated, and the force data were detected. Hence, force feedback was realized in the experiment. CONCLUSIONS: The surgical robot can help surgeons to complete trajectory motions with haptic sensation.